Beat Browser

Thesis (S.M.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2007.Includes bibliographical references (p. 51-53).Beat Browser is a music browsing environment that delivers immediate audio feedback while browsing arbitrarily large music collections. The goal of Beat Browser is to give users a sense of exploring "live" and continuous audio while rapidly moving between sources by mouse. It appears their entire universe of music is playing all the time, whether they're there listening or not. Beat Browser's Universal Time Base architecture keeps a central clock running that manages the playback position of every piece of music launclied, orchestrating this perceptual illusion.by Jefferey D. Goldenson.S.M

Characterizing Polytobacco Use Trajectories and Their Associations With Substance Use and Mental Health Across Mid-Adolescence.

Background:Polytobacco product use is suspected to be common, dynamic across time, and increase risk for adverse behavioral outcomes. We statistically modeled characteristic types of polytobacco use trajectories during mid-adolescence and tested their prospective association with substance use and mental health problems. Methods:Adolescents (N = 3393) in Los Angeles, CA, were surveyed semiannually from 9th to 11th grade. Past 6-month combustible cigarette, e-cigarette, or hookah use (yes/no) over four assessments were analyzed using parallel growth mixture modeling to identify a parsimonious set of polytobacco use trajectories. A tobacco product use trajectory group was used to predict substance use and mental health at the fifth assessment. Results:Three profiles were identified: (1) tobacco nonusers (N = 2291, 67.5%) with the lowest use prevalence (<3%) of all products across all timepoints; (2) polyproduct users (N = 920, 27.1%) with moderate use prevalence of each product (8-35%) that escalated for combustible cigarettes but decreased for e-cigarettes and hookah across time; and (3) chronic polyproduct users (N = 182, 5.4%) with high prevalence of each product use (38-86%) that escalated for combustible cigarettes and e-cigarettes. Nonusers, polyproduct users, and chronic polyproduct users reported successively higher alcohol, marijuana, and illicit drug use and ADHD at the final follow-up, respectively. Both tobacco using groups (vs. nonusers) reported greater odds of depression and anxiety at the final follow-up but did not differ from each other. Conclusions:Adolescent polytobacco use may involve a common moderate risk trajectory and a less common high-risk chronic trajectory. Both trajectories predict substance use and mental health symptomology. Implications:Variation in use and co-use of combustible cigarette, e-cigarette, and hookah use in mid-adolescence can be parsimoniously characterized by a small set common trajectory profiles in which polyproduct use are predominant patterns of tobacco product use, which predict adverse behavioral outcomes. Prevention and policy addressing polytobacco use (relative to single product use) may be optimal tobacco control strategies for youth, which may in turn prevent other forms of substance use and mental health problems

Targeting megakaryocytic induced fibrosis by AURKA inhibition in the myeloproliferative neoplasms

Primary myelofibrosis (PMF) is characterized by bone marrow fibrosis, myeloproliferation, extramedullary hematopoiesis, splenomegaly and leukemic progression. Moreover, the bone marrow and spleen of patients are full of atypical megakaryocytes that are postulated to contribute to fibrosis through the release of cytokines including TGF-β. Although the JAK inhibitor ruxolitinib provides symptomatic relief, it does not reduce the mutant allele burden or significantly reverse fibrosis. Here we show through pharmacologic and genetic studies that, apart from JAK2, Aurora kinase A (AURKA) is a novel therapeutic target in PMF. MLN8237, a selective AURKA inhibitor promoted polyploidization and differentiation of PMF megakaryocytes and displayed potent anti-fibrotic and anti-tumor activity in vivo. We also reveal that loss of one allele of AURKA is sufficient to ameliorate fibrosis and other PMF phenotypes in vivo. Our data suggest that megakaryocytes are drivers of fibrosis and that targeting them with AURKA inhibitors will provide therapeutic benefit in PMF

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Atmospheric River Tracking Method Intercomparison Project (ARTMIP): project goals and experimental design

The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis from January 1980 to June 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High-resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here, we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month proof-of-concept trial run designed to illustrate the utility and feasibility of the ARTMIP project